Post-treatment Counts Research Articles

The association between total lymphocyte count after concomitant chemoradiation and overall survival in patients with newly diagnosed glioblastoma

Several studies have been conducted to determine the relationship between post-treatment total lymphocyte count (TLC) and overall survival (OS) in patients with malignant tumors including glioblastomas (GBMs). In this retrospective study, whether patients with newly diagnosed GBM experience significant lymphopenia after concomitant chemoradiation (CCRT) was evaluated, and whether TLC after this treatment is associated with OS in the treated population was examined. Using electronic medical records, all patients newly diagnosed with GBM between 2008 and 2016 at Seoul St. Mary’s Hospital were retrospectively examined. The eligible criteria included the following: 1) craniotomy with surgical resection or biopsy, 2) completion of CCRT, 3) accessible baseline and/or follow-up complete blood count (CBC). Median TLC significantly decreased after completion of CCRT, compared to TLC at baseline (1742 versus 1319 cells/mm3, P-value < 0.001). Patients with TLC < 1200 cells/mm3 at 4 weeks after the completion of CCRT showed shorter survival than those with TLC ≥ 1200 cells/mm3 with median OS of 14.5 versus 21.0 months (P-value = 0.017). Also, in multivariate analysis for OS, TLC < 1200 cells/mm3 at 4 weeks after the completion of CCRT (HR 1.97, 95% CI 1.61 – 2.25, P-value = 0.004) were significantly associated with shorter survival. The results from the present study indicate that treatment-related total lymphocyte counts after CCRT is associated with worse survival in patients with newly diagnosed GBM.

Lintuzumab Ac-225 in Combination with CLAG-M Chemotherapy in Relapsed/Refractory AML: Interim Results of a Phase I Study

Background: Lintuzumab Ac225 is a radiolabeled anti-CD33 antibody with demonstrated single-agent activity in AML. The drug is composed of an alpha emitting isotope, Ac225, conjugated with the humanized anti-CD33 monoclonal antibody lintuzumab. In a prior study, lintuzumab Ac225 monotherapy was safely administered to elderly/unfit AML patients with toxicities primarily limited to prolonged myelosuppression. Nearly 70% of patients achieved a CR/CRi at the highest dose level (2uCi/kg). We hypothesized that lintuzumab Ac225, when added to the salvage chemotherapy regimen CLAG-M (cladribine, cytarabine, G-CSF, and mitoxantrone), would be tolerable and would improve remission rates in the treatment of relapsed/refractory AML (RR-AML). CLAG-M salvage was selected based on favorable institutional outcomes (CR/CRi: 54%, Mushtaq et al, ASH 2018). This novel investigator-initiated phase I study is the first study to combine radioimmunotherapy and intensive chemotherapy in patients with RR-AML. Patients and Methods: Eligible patients include medically fit, RR-AML patients aged 18 years and older, with adequate organ function. In addition, more than 25% of leukemic blasts must have been CD33 positive by flow cytometry. Induction consisted of G-CSF, 300mcg/d, given D1-6, cladribine 5mg/m2, given D2-6, cytarabine 2g/m2, given D2-6, and mitoxantrone 10mg/m2, given D2-4. Lintuzumab Ac225 was administered as a single dose on either days 7, 8, or 9. Cohort 1 received lintuzumab Ac225 at a dose of 0.25uCi/kg, and cohort 2 received a dose of 0.50uCi/kg. Only one induction course was administered, and subsequent treatments were up to physician discretion. Results: Nine patients with a median age of 59 years (range 47-73 yrs) have been enrolled. Patients had a median of 2 (range 1-4) prior, anti-leukemic treatments, including 4 patients who relapsed following allogeneic HCT. Four patients (44%) had intermediate risk cytogenetics, and five patients (56%) had adverse risk features. Median blast CD33 expression was 73% (range 32-100%). All patients completed one cycle of lintuzumab Ac225 with CLAG-M. Three patients enrolled into cohort 1 (0.25mcg/kg), and six patients enrolled into cohort 2 (0.5mcg/kg). Among all enrolled patients, Grade 3 or greater AEs include febrile neutropenia (n=4), infection (n=4), QTc prolongation (n=1), hypophosphatemia (n=1), hyponatremia (n=1), and tumor lysis syndrome (n=1). In two responding patients enrolled to cohort 2, one patient had prolonged time to neutrophil recovery (ANC&gt;500 at 53 days), and a second patient, who was post-HCT, had an ANC recovery to 300 by day 42, and then received donor CD34+ stem cells to aide in count recovery. Figure 1 summarizes toxicities. All responding patients with a platelet count&gt;50k prior to therapy, had a post-treatment platelet count &gt;50k within 42 days. No mortalities were observed on study. Among cohort 1 patients (n=3), one patient achieved CR, one patient had a &gt;50% blast reduction to 6.2% blasts with neutrophil recovery and platelet improvement to 70k, and the third patient had no response. Overall, 33% (1/3) achieved a CR. Among patients enrolled into cohort 2, two patients achieved CR, two patients achieved CRp, one patient achieved CRi, and one patient had no response. Overall, 83% (5/6), achieved CR/CRp/CRi. After, three patients on study subsequently went onto allogeneic HCT, two patients initiated donor lymphocyte infusions (DLI), and one patient underwent CD34+ stem cell boost. Conclusion: Combining lower doses of lintuzumab Ac225 with salvage CLAG-M chemotherapy appears to have a clinically acceptable safety profile. With dose escalation, increased myelosuppression has been noted alongside, but also highly encouraging efficacy results for RR-AML. As two patients in Cohort 2 met DLT criteria due to prolonged ANC recovery, this study will be amended to mandate the addition of G-CSF two weeks after Lintuzumab Ac225 treatment. Tentatively, this study will plan to extend the ANC recovery observation period to 60 days. Depending on safety and further efficacy data, this may lead to further dose escalation, or potentially an expanded number of patients in a Phase 2 study. Disclosures Abedin: Actinium Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Honoraria; Agios: Honoraria; Helsinn Healthcare: Research Funding; Pfizer Inc: Research Funding. Runaas:Agios: Honoraria; Blueprint Medicine: Honoraria. Michaelis:Incyte: Consultancy, Research Funding; Novartis: Consultancy; BMS: Research Funding; TG Therapeutics: Consultancy, Research Funding; JAZZ: Other: Data Safety Monitoring Board, uncompensated, Research Funding; Macrogeneics: Research Funding; Millenium: Research Funding; ASTEX: Research Funding; Pfizer: Equity Ownership, Research Funding; Celgene: Consultancy, Research Funding; Bioline: Research Funding; Janssen: Research Funding. Atallah:Helsinn: Consultancy; Jazz: Consultancy; Takeda: Consultancy, Research Funding; Pfizer: Consultancy; Jazz: Consultancy; Helsinn: Consultancy; Novartis: Consultancy. Hamadani:Celgene: Consultancy; Merck: Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau; Otsuka: Research Funding; Janssen: Consultancy; Medimmune: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Research Funding; Takeda: Research Funding; Pharmacyclics: Consultancy.

ATIM-35. THE ASSOCIATIONS BETWEEN TOTAL LYMPHOCYTE COUNTS AFTER CONCOMITANT CHEMORADIATION WITH OVERALL SURVIVAL IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

Abstract Several studies have been conducted to determine the relationship between post-treatment total lymphocyte count (TLC) and overall survival (OS) in patients with malignant tumors including glioblastomas (GBMs). In this retrospective study, whether patients with newly diagnosed GBM experience significant lymphopenia after concomitant chemoradiation (CCRT) was evaluated, and whether TLC after this treatment is associated with OS in the treated population was examined. Using electronic medical records, all patients newly diagnosed with GBM between 2008 and 2016 at Seoul St. Mary’s Hospital were retrospectively examined. The eligible criteria included the following: 1) craniotomy with surgical resection or biopsy, 2) completion of CCRT, 3) accessible baseline and/or follow-up complete blood count (CBC). Median TLC significantly decreased after completion of CCRT, compared to TLC at baseline (1,742 versus 1,319 cells/mm3, P-value &amp;lt; 0.001). Patients with TLC &amp;lt; 1,200 cells/mm3 at 4 weeks after the completion of CCRT showed shorter survival than those with TLC ≥ 1,200 cells/mm3 with median OS of 14.5 versus 21.0 months (P-value = 0.017). Also, in multivariate analysis for OS, TLC &amp;lt; 1,200 cells/mm3 at 4 weeks after the completion of CCRT (HR 1.97, 95% CI 1.61 – 2.25, P-value = 0.004) were significantly associated with shorter survival. The results from the present study indicate that treatment-related total lymphocyte counts after CCRT is associated with worse survival in patients with newly diagnosed GBM.

889P - Circulating tumour cells (CTC) count and prostate-specific antigen (PSA) response measures in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with docetaxel (Doc)

BackgroundClinically meaningful measures of response are needed in mCRPC. Post-treatment CTC decline have shown to be superior to PSA response in determining outcome in pts treated with AR signalling inhibitors. We compared the performance of CTC and PSA measures of response in mCRPC Doc-treated pts. MethodsBaseline and post-treatment (6 to 9 weeks) CTC of mCRPC pts treated with Doc at first or second-line in a prospective study were determined with CellSearchTM platform. CTC response was defined: 30% decline from baseline (CTC30%), conversion (≥5 to<5; CTCConv) or decline to 0 CTC in pts with >0 baseline CTC (CTC0). PSA response was determined at 12w as 30% (PSA30) or 50% decline (PSA50) from baseline. Cox-regression model were used to evaluate the association of baseline CTC (BLCTC), CTC response and PSA response measures with overall survival (OS), progression-free survival (PFS) or time to PSA progression (TTPP). C-index were used to evaluate the performance of each of the Cox regression model. Results80 pts had evaluable BLCTC, 52 had evaluable post-treatment CTC count. Of 80 eligible pts, 53 (66.3%) received Doc at first-line. Median OS was 19 m (95%CI:16.4-21.8); median BLCTC was 7. BLCTC were associated with bone mts, higher PSA, ALP and LDH, and lower albumin levels. BLCTC was associated with OS (HR: 3.5; p<0.001), PFS (HR: 1.98; p=0.001) and TTPP (HR: 1.8; p=0.001). CTC (CTC30%, CTCConv, CTC0) but not PSA (PSA30, PSA50) response measures were significantly associated with OS. C-index values were higher for CTC resp endpoints (Table). 24 pts had discordant PSA30 and CTC30% response; longer OS (18.4 vs 8.4m; p=0.188) was observed in pts with CTC30% resp, without PSA30 resp.Table889PTableN (%)HR (95%CI); p-valueC-indexCTC Conv27 (51.9)0.33 (0.18-0.60); p<0.0010.665CTC08 (15.4)0.26 (0.10-0.67); p=0.0050.602CTC30%34 (65.4)0.33 (0.18-0.61); p<0.0010.644PSA3032 (61.5)0.72 (0.40-1.30); p=0.2710.563PSA5022 (42.3)0.68 (0.38-1.20); p=0.1830.595 ConclusionsBaseline CTC were associated with OS, PFS and TTPP. CTC response measures were significantly associated with outcome, and showed a greater performance than PSA response measures in mCRPC Doc-treated pts. Legal entity responsible for the studySpanish National Cancer Research Center (CNIO) and The Institute of Cancer Research (ICR). FundingHas not received any funding. DisclosureR. Lozano Mejorada: Honoraria (self): Roche, Janssen-Cilag, Bayer; Research grant / Funding (institution): Bayer, Janssen-Cilag; Travel / Accommodation / Expenses: Roche, Janssen-Cilag, Astellas Pharma. D. Lorente: Honoraria (self): Janssen-Cilag, Bayer, Astellas Pharma, Sanofi; Advisory / Consultancy: Janssen-Cilag, Bayer, Sanofi; Travel / Accommodation / Expenses: Sanofi, Astellas, Janssen-Cilag, Celgene. E. Castro: Honoraria (self): Astellas Pharma, Janssen-Cilag, AstraZeneca, Bayer, Pfizer; Advisory / Consultancy: Bayer, Janssen-Cilag, AstraZeneca, Clovis Oncology; Research grant / Funding (institution): Janssen-Cilag, AstraZeneca, Bayer; Travel / Accommodation / Expenses: Bayer, Janssen-Cilag, Roche, Astellas Pharma. N. Romero Laorden: Honoraria (self): MSD, Sanofi-Aventis, Astellas, Janssen-Cilag; Travel / Accommodation / Expenses: Bayer, Janssen-Cilag, Roche, PharmaMar; Research grant / Funding (institution): Bayer, Astellas, Janssen-Cilag, Sanofi-Aventis. E. Almagro Casado: Honoraria (self): MSD; Travel / Accommodation / Expenses: BMS. M. Saez: Honoraria (self): Bristol-Myers Squibb, Pfizer, Novartis, Bayer, Janssen-Cilag, Sanofi-Aventis, Astellas Pharma, Ipsen, EUSA Pharma; Advisory / Consultancy: Bristol-Myers Squibb, Pfizer, Novartis, Bayer, Janssen-Cilag, Sanofi-Aventis, Astellas Pharma, Ipsen, EUSA Pharma; Travel / Accommodation / Expenses: Bristol-Myers Squibb, Pfizer, Novartis, Bayer, Janssen-Cilag, Sanofi-Aventis, Astellas Pharma, Ipsen, EUSA Pharma. D. Olmos Hidalgo: Honoraria (self): Janssen-Cilag, Bayer, Sanofi; Advisory / Consultancy: Bayer, Janssen-Cilag, AstraZeneca, Clovis Oncology; Research grant / Funding (institution): Bayer, Janssen-Cilag, AstraZeneca, Roche/Genentech, Medications/Pfizer, Astellas, Tokai, MSD, GSK; Travel / Accommodation / Expenses: Bayer, Janssen-Cilag, Ipsen. All other authors have declared no conflicts of interest.

Association Between Circulating Lymphocyte Populations and Outcome After Stereotactic Body Radiation Therapy in Patients With Hepatocellular Carcinoma.

Background and Objective: Radiation-induced lymphopenia has a tangible impact on overall survival (OS) in multiple solid tumors. We investigated the association between circulating lymphocyte populations (CLPs) before and after stereotactic body radiation therapy (SBRT) and OS in patients with hepatocellular carcinoma (HCC).Materials and Methods: Seventy-eight HCC patients treated with SBRT between January 2013 and June 2017 were retrospectively analyzed. Baseline and post-treatment total peripheral lymphocyte counts (TPLCs) and values of different CLPs were obtained and analyzed for clinical outcomes. Univariate and multivariate Cox regression analyses were used to explore the independent prognostic factors for patient survival.Results: The one-, two- and three-year OS rates were 94.8, 75.9, and 63.3%, respectively. The mean TPLCs before and 10 days after SBRT were 1.4 × 109/L and 0.7 × 109/L, respectively. The TPLC recovered to its baseline value 1 year after SBRT. Multivariate analysis results revealed that variables, including tumor necrosis factor-alpha (TNF-α) level <5.5 ng/mL and post-treatment TPLC <0.45 × 109/L were independent factors for inferior OS. Further analysis showed that the values of CLPs, including CD3+, CD4+, CD8+, CD19+, and CD16+56+ cells dropped profoundly 10 days after SBRT, among which CD19+ B cell count was mostly depleted and gradually recovered after 2 months. Univariate analysis showed that both baseline and post-treatment TPLC and CLP (except post-treatment B cell) counts were significantly associated with patient OS (p < 0.05 for each). Further stratified analysis performed according to OS at 2 years demonstrated that the CD16+CD56+ NK cell counts remained significantly elevated in patients with better survival (OS > 2 years) compared to those in short-term survivors at 10 days, 1 month, and 2 months after SBRT (p < 0.05 for each). In addition, there were significant differences in TPLC and CD8+ T cell counts in patients with long-term and short-term OS at 2 months after SBRT (p < 0.05).Conclusions: Peripheral lymphopenia after SBRT might be an independent prognostic factor for poorer outcome in HCC patients. Post-treatment lymphocyte subsets, including CD8+ T cell and NK cell counts were also associated with 2-year OS rates.

Post-Treatment ANC is Predictive of Poorer Overall Survival and Disease-Free Survival in Esophageal Cancer Patients after Tri-Modality Therapy

Although neutrophils serve important roles in inflammation and host defense, increasing evidence points towards their involvement in tumorigenesis and progression. Recent studies show that increased pre-treatment neutrophils associate with disease recurrence and survival rates in esophageal cancer. Here, we evaluate the association of post-treatment absolute neutrophil count (ANC) with survival outcomes in primary non-metastatic esophageal cancer patients who have received tri-modality therapy. We reviewed 219 consecutive patients with stage I-III esophageal cancer who completed tri-modality therapy at our center between 1/2007 and 12/2015. Of the 219 patients, 123 completed all treatments within 5 months of starting radiation and had available ANC at 6 months after start of radiation (range: +/- 1 month). 70 (57%) were > 60 years old, and 110 (89%) were male. 116 (94%) tumors were adenocarcinoma, 89 (72%) were stage III, and 120 (98%) were located distally. 120 (98%) received induction chemotherapy of which 77 (64%) received platinum-taxane (PT). All received concurrent chemotherapy of which 69 (56%) received PT. 90 (73%) had the same induction and concurrent agents. 118 (96%) received intensity modulated radiation therapy, with median dose of radiation being 5040cGy in 28 fractions (range: 4320-5600cGy). Kaplan-Meier survival, log-rank tests, and multivariate Cox regression were used to analyze the association of ANC with survival outcomes. The median follow up was 31 months (range: 5.7-119.9 months). Multivariate Cox regression using age, gender, KPS, stage, histology, tumor location, time to surgery, induction PT, concurrent PT, lung V20, mean heart dose, PTV size, and pre- and post-treatment ANC showed that increased 6-month ANC was predictive of worse overall survival/OS (p=0.0001, HR 1.3). The median ANC was 3.9 K/microliter (range: 0.9-30.4). When stratified by median ANC, patients with ANC > 3.9 had significantly worse OS compared to those with ANC ≤ 3.9 (5-year OS=35% vs 57%, p=0.049), and the disease-free survival (DFS) was also worse although this was not significant (5-year DFS=11% vs 24%, p=0.09). Subgroup analysis showed that the predictive value of ANC is influenced by choice of concurrent chemotherapy agent. In patients receiving concurrent non-PT, ANC > 3.9 predicted for worse 5-year OS (25% vs 57%, p=0.024) and 5-year DFS (4% vs 30%, p=0.022). This relationship was not seen for concurrent PT. Higher post-treatment ANC is predictive of poorer survival in primary non-metastatic esophageal cancer patients who have received tri-modality therapy, and this effect is influenced by choice of concurrent chemotherapy agent. Further investigation could consider individual neutrophil subpopulations, how they are affected by different treatment regimens, and their roles in cancer progression.

Abstract CT097: Phase I trial of apalutamide plus abiraterone acetate, docetaxel, and prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC)

Abstract Background: Prostate cancer is driven by the androgen receptor (AR) pathway, which may be targeted by inhibition of androgen synthesis (e.g. abiraterone = Abi), AR signaling (e.g. apalutmide = Apa), and/or translocation of AR to the nucleus (e.g. docetaxel = Doce). The combination of AR inhibition plus taxane chemotherapy has already demonstrated clinical benefit (CHAARTED, STAMPEDE), lending weight to the theory that combining drugs targeting different points in the AR signaling pathway is effective. We hypothesize that the combination of Apa, Abi, and Doce will be safe and efficacious. Methods: Men with progressive mCRPC, intact organ function, and no prior exposure to Apa (ever) or Doce within 3 years were enrolled. Standard Abi 1000 mg daily, Doce 75 mg/m2 q3 weeks, and prednisone 5 mg BID was administered with different doses of Apa. Cohort 1 = Apa 120 mg daily, Cohort 2 = Apa 240 mg daily, Cohort 3 (if necessary) = Apa 180 mg daily in modified 3+3 design. The primary endpoint of the Phase I dose-escalation portion of the study was determination of dose-limiting toxicity (over 6 weeks) and recommended Phase II dose (RP2D). Results: Nine men (3 Apa 120 mg, 6 Apa 240 mg) with mCRPC and median age 69, median PSA 8.18 (range 0.07 - 278.5) were treated. 67% with bone, 78% LN, 11% lung, 11% other metastases. No DLT occurred with Apa 120 mg and 1 of 6 with Apa 240 mg had possibly related grade 3 hypertension. All had &amp;gt;95% PSA decline (78% with &amp;gt; 99% decline). Of 5 with measureable disease, 100% had RECIST response. 6 of 7 with post-treatment CTC counts were undetectable. Conclusions: The combination of apalutamide plus abiraterone, docetaxel, and prednisone at full doses is tolerable, with the RP2D of the regimen Apa 240 mg daily, Abi 1000 mg daily, docetaxel 75 mg/m2 q3 wks, and prednisone 5 mg BID. The combination appears to be associated with a high rate of PSA decline, measurable disease response, and CTC count control. Tumor tissue, plasma ctDNA, and CTCs are being collected for analysis. Enrollment to the expansion phase of study to further refine efficacy and toxicity at PCCTC sites is ongoing including assessment of response and resistance biomarkers [NCT02913196] Citation Format: Ana Molina, Paul Christos, Amy Hackett, Luke Nordquist, Edward Gelmann, Mark Stein, Cora Sternberg, Himisha Beltran, Lauren Gracey, Giuseppe Galletti, Paraskevi Giannakakou, David M. Nanus, Scott T. Tagawa. Phase I trial of apalutamide plus abiraterone acetate, docetaxel, and prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT097.

Factors affecting differential outcomes in the definitive treatment of anal cancer between HIV+ and HIV- patients.

3572 Background: Anal cancer is an uncommon malignancy with numerous factors that influence treatment outcomes. Historically, HIV+ patients were restricted from entering clinical trials, limiting data on their outcomes to small retrospective reports. This study seeks to understand the factors related to anal cancer outcomes, specifically the differences between HIV+ and HIV- patients. Methods: Inclusion criteria was non-metastatic anal squamous cell carcinoma treated with a definitive course of chemotherapy and radiation between 2005 and 2018 at a single institution. Clinical data related to baseline characteristics, treatment parameters, and post-treatment follow-up were extracted for calculation of freedom from local recurrence (FFLR) and overall survival (OS). Univariate analysis (UVA) and multivariate analysis (MVA) were done using cox proportional hazard model, and FFLR and OS were calculated using the Kaplan-Meier method. Results: During the study period, 111 patient initiated definitive treatment for anal cancer. Median age was 56.7 years (IQR: 51.4-63.5), and 47% (N = 52) were HIV+. At median follow-up of 28 months, 12 and 24-month FFLR was 84.1% and 78.2% respectively, with 24-month OS of 87.3%. MVA demonstrated significant association between FFLR and T-stage HR 4.02 (95% CI: 2.14-7.55) p &lt; 0.001, elapsed treatment time (median of 50 days) 1.08 (95% CI: 1.04-1.12) p &lt; 0.001, and diagnosis to treatment start (median time of 15 weeks) 1.05 (95% CI: 1.01-1.08) p = 0.005. Additional analysis with log-rank test for FFLR demonstrated significant difference between patients taking &lt; 50 days to complete treatment (p = 0.03), and &lt; 15 weeks from diagnosis to treatment completion (p = 0.006). In HIV+ patients, post-treatment CD4 &lt; 150 was significantly associated with worse OS on log-rank test (p = 0.016), with pretreatment CD4 values being non-significant. Conclusions: This study represents the largest single institution report of HIV positive patients treated for anal cancer. No difference in local recurrence or overall survival between HIV+ and HIV- patients was elucidated; however, HIV+ patients with lower post-treatment CD4 counts had worse OS. The most significant predictors of local recurrence were advanced T-stage, increased time from diagnosis to treatment initiation, and prolonged treatment time.

Post-treatment lymphocytopaenia, integral body dose and overall survival in lung cancer patients treated with radical radiotherapy

IntroductionPost-treatment lymphocytopaenia is a recognized complication of thoracic radiotherapy likely due to irradiation of a large volume of circulatory blood. We hypothesize that post-treatment absolute lymphocyte count (ALC) is associated with integral body dose and overall survival (OS) in lung cancer patients treated with radical radiotherapy. Materials and methodsData on clinicopathological variables, dosimetric parameters, and pre and post-treatment blood counts were collected retrospectively in 217 lung cancer patients (131 with non-small cell lung cancer and 86 with small cell lung cancer) treated with radical radiotherapy. Induction chemotherapy followed by radiotherapy and concurrent chemoradiotherapy were delivered in 89 (42%) and 99 (47%) patients respectively. Multiple stepwise regression analysis was performed separately for ALC and absolute neutrophil count (ANC) to derive a model for prediction of post-treatment count and multivariate analysis was performed for OS using a Cox regression model. ResultsThere was a significant decline in post-treatment counts for both ANC and ALC (p < 0.001). Multiple stepwise linear regression analysis confirmed pre-treatment ALC, body integral dose and use of concurrent chemotherapy as significant predictors of post-treatment ALC (R2 = 0.33, F(4,212) = 26.6 p < 0.001). Pre-treatment ANC, integral heart dose and number of fractions were significant predictors of post-treatment ANC (R2 = 0.18, F(3,213) = 16.38 p < 0.001). Low post-treatment ALC, high pre-treatment ANC, high planning target volume integral dose and lower number of fractions were predictive of inferior OS. ConclusionsThere is a negative correlation between integral body dose and post-treatment ALC which is an adverse prognostic factor in lung cancer patients treated with radical radiotherapy.

Management of the Invasive Shrub Amur Honeysuckle (Lonicera maackii) for the Endangered Perennial Wild Dill (Perideridia americana)

AbstractRadnor Lake State Natural Area in Nashville, TN, has cedar glades that contain the endangered perennial herb wild dill [Perideridia americana (Nutt. ex DC.) Rchb.] and the invasive shrub Amur honeysuckle [Lonicera maackii (Rupr.) Herder]. This research examined whether L. maackii treatment in the Radnor Lake State Natural Area cedar glades is followed by an increase in P. americana plants. A grid of 60 adjacent 2 m by 4 m plots was placed in five cedar glades to encompass the P. americana population. With great care to protect P. americana, the annual treatment for L. maackii was to pull plants ≤1-m tall from the ground; and to cut stems &gt;1-m tall and then treat the stumps with glyphosate. The t-tests of means for the log natural of the number of plants in the 60 plots (significance level of P-value = 0.05) were used to compare pretreatment L. maackii and P. americana counts with posttreatment counts in 2018 and P. americana counts at leaf out and flowering in 2018. The L. maackii population was significantly smaller (P-value &lt; 0.001) in 2018 than pretreatment at all five sites. When pretreatment in 2014 and 2015 was compared with posttreatment in 2018 for the P. americana populations, the increases were significant at the Cheek, Harris 2, Hideaway, and Norfleet sites, but the increase at East Hall Farm was not significant. White-tailed deer (Odocoileus virginianus Zimmermann) trampling was the explanation given for the decreases in P. americana from leaf out to flowering at all five sites in 2018. Browsing was evident only at Hideaway, which had a greater loss for P. americana from leaf out to flowering in 2018 than the combined losses for the Cheek, East Hall Farm, Harris 2, and Norfleet sites. The research informed the creation of adaptive management decisions regarding monitoring and treatment of the invasive species L. maackii for an endangered species.

Pulsed Transcranial Red/Near-Infrared Light Therapy Using Light-Emitting Diodes Improves Cerebral Blood Flow and Cognitive Function in Veterans with Chronic Traumatic Brain Injury: A Case Series.

Objective: This study explored the outcome of applying red/near-infrared light therapy using light-emitting diodes (LEDs) pulsed with three different frequencies transcranially to treat traumatic brain injury (TBI) in Veterans.Background: Photobiomodulation therapy (PBMT) using LEDs has been shown to have positive effects on TBI in humans and animal models.Materials and methods: Twelve symptomatic military Veterans diagnosed with chronic TBI >18 months post-trauma received pulsed transcranial PBMT (tPBMT) using two neoprene therapy pads containing 220 infrared and 180 red LEDs, generating a power output of 3.3 W and an average power density of 6.4 mW/cm2 for 20 min, thrice per week over 6 weeks. Outcome measures included standardized neuropsychological test scores and qualitative and quantitative single photon emission computed tomography (SPECT) measures of regional cerebral blood flow (rCBF).Results: Pulsed tPBMT significantly improved neuropsychological scores in 6 of 15 subscales (40.0%; p < 0.05; two tailed). SPECT analysis showed increase in rCBF in 8 of 12 (66.7%) study participants. Quantitative SPECT analysis revealed a significant increase in rCBF in this subgroup of study participants and a significant difference between pre-treatment and post-treatment gamma ray counts per cubic centimeter [t = 3.77, df = 7, p = 0.007, 95% confidence interval (95,543.21–21,931.82)]. This is the first study to report quantitative SPECT analysis of rCBF in regions of interest following pulsed tPBMT with LEDs in TBI.Conclusions: Pulsed tPBMT using LEDs shows promise in improving cognitive function and rCBF several years after TBI. Larger, controlled studies are indicated.

The Efficacy of Ostrich Antibodies to Dihydrotestosterone and 5&amp;lt;i&amp;gt;α&amp;lt;/i&amp;gt;-Reductase in the Restoration of Hair Growth

The hormone dihydro testosterone (DHT) and the catalyst 5α-reductase are key contributors to hair loss due to androgenetic alopecia (AGA). Also, dermal bacteria and their toxins have been implicated in hair loss. A preliminary study by the authors with six male volunteer subjects showed that ostrich antibodies against above causative substances were quite effective in promoting hair regrowth. The present study included 13 men and 4 women, with ages ranging from 39 to 78. Pre- and post-treatment hair counts were also incorporated into the study procedure. In all instances but one, the subjects had a hair-growth effect about 3 months after the antibody was applied to the scalp, and the study participants with hair growth were pleased with the results and with the ease of use of the antibody solution.

Exploring the anti-allergic property of potentized sodium chloride using nasal eosinophil count as a criterion

Background: Nasal eosinophilia is a specific and valuable means for diagnosing and predicting the prognosis of allergic rhinitis (AR). Evidence-based recommendation for treating AR with homeopathic medicines is lacking. Symptomatology of Natrum Muriaticum (NM) derived from homeopathic pathogenetic trials and clinical proving aids its wide use in practice. Objective: The study aided in ascertaining the anti-allergic property of NM in lowering the nasal eosinophil count in patients with AR. Methods: This prospective, observational study included patients diagnosed with AR along with nasal eosinophilia, provided they received NM 30C homeopathic remedy. Written consent was obtained from 15 patients and then included in the study. Nasal smear was collected on the first visit before the treatment and at the end of 2 weeks after the treatment. Statistical Analysis and Results: Pre- and post-treatment nasal eosinophil counts were statistically analyzed using the paired t-test. The difference in mean eosinophil count (0.06333) was statistically significant, where P

Pulsed Transcranial Red/Near-Infrared Light Therapy Using Light-Emitting Diodes Improves Cerebral Blood Flow and Cognitive Function in Veterans with Chronic Traumatic Brain Injury: A Case Series.

This study explored the outcome of applying red/near-infrared light therapy using light-emitting diodes (LEDs) pulsed with three different frequencies transcranially to treat traumatic brain injury (TBI) in Veterans. Photobiomodulation therapy (PBMT) using LEDs has been shown to have positive effects on TBI in humans and animal models. Twelve symptomatic military Veterans diagnosed with chronic TBI >18 months post-trauma received pulsed transcranial PBMT (tPBMT) using two neoprene therapy pads containing 220 infrared and 180 red LEDs, generating a power output of 3.3 W and an average power density of 6.4 mW/cm2 for 20 min, thrice per week over 6 weeks. Outcome measures included standardized neuropsychological test scores and qualitative and quantitative single photon emission computed tomography (SPECT) measures of regional cerebral blood flow (rCBF). Pulsed tPBMT significantly improved neuropsychological scores in 6 of 15 subscales (40.0%; p < 0.05; two tailed). SPECT analysis showed increase in rCBF in 8 of 12 (66.7%) study participants. Quantitative SPECT analysis revealed a significant increase in rCBF in this subgroup of study participants and a significant difference between pre-treatment and post-treatment gamma ray counts per cubic centimeter [t = 3.77, df = 7, p = 0.007, 95% confidence interval (95,543.21-21,931.82)]. This is the first study to report quantitative SPECT analysis of rCBF in regions of interest following pulsed tPBMT with LEDs in TBI. Pulsed tPBMT using LEDs shows promise in improving cognitive function and rCBF several years after TBI. Larger, controlled studies are indicated.

Appraisal of Basic-Hemostatic Markers in Lung Cancer Patients During Follow-Up Care After Radiotherapy Treatment.

BackgroundThe aim of this paper was to investigate the association between clinicopathological factors and the coagulation test in lung cancer patients during follow-up care after treatment.Material/MethodsNinety-five medical patients with histologically proven advanced lung carcinoma (LC) who had undergone radiotherapy were prospectively reviewed between January 2014 and December 2016. The study investigated the relationship between the biochemical results, the disease stage, and the survival rate in lung cancer patients. Post-treatment coagulation-based D-dimer (DD), fibrinogen (Fib), and complete blood count (CBC) were evaluated during the follow-up over a period of 2 years after treatment or until the patient’s death.ResultsAn increase of D-dimer generates an increased chance of early death by approximately 0.03% per 1 D-dimer unit. In cases when the difference in the D-dimer concentration equals 1000, the risk of an early death increases by (1.00031000−1)×100%=35%.ConclusionsHigh levels of D-dimer are associated with an advanced form of disease with metastasis and higher risk of early death in lung cancer patients.

A post marketing randomized placebo controlled study to evaluate the efficacy of study product UPLAT® (Carica papaya leaf extract + Tinospora cordifolia extract) in the cancer patients with thrombocytopenia induced by chemotherapy

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Thrombocytopenia refers to abnormal decrease in platelet count in an individual. The condition may rise at different grades of severity in cancer patients under chemotherapy. In most of the cases, thrombocytopenic condition of cancer patient becomes a major therapy limiting factor. Generally, the treatment of thrombocytopenia lies in dose reduction and/or dose delay but this may adversely affect the treatment plan of cancer. Therefore, managing chemotherapy induced thrombocytopenia is still a challenge. This study was conducted to examine the platelet count improving effect of marketed product UPLAT® (&lt;em&gt;Carica papaya&lt;/em&gt; leaf extract + &lt;em&gt;Tinospora cordifolia&lt;/em&gt; extract) in cancer patients with chemotherapy induced thrombocytopenia (CIT).&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; Fourty (40) subjects were recruited as ‘case’ and twenty (20) as ‘control’. ‘Cases’ were cancer patients with chemotherapy induced thrombocytopenia. UPLAT® containing following active ingredients; &lt;em&gt;Carica papaya&lt;/em&gt; leaf extract: 350 mg (standardized to 2% flavonoids) and &lt;em&gt;Tinospora cardifolia&lt;/em&gt; extract: 150 mg (standardized to 3% bitters) was given twice daily (2 units each) for 10 consecutive days. Platelet count was observed at baseline and day 15 (end of the study). Then pre and post-treatment platelet counts were compared individually in both arms by statistical tests. Response was evaluated in fourty (40) ‘cases’ and twenty ‘control’y.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; Mean change for platelet count in case group (93990.00±63896.73) was much higher than control group (27600.00±29758.42). No adverse events with the treatment were observed.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study proves the effectiveness of platelet booster UPLAT® (combination of &lt;em&gt;Carica papaya&lt;/em&gt; leaf extract and &lt;em&gt;Tinospora cordifolia&lt;/em&gt;) as it significantly increased thrombocytes/platelet count in post-chemotherapy cancer patients.&lt;/p&gt;&lt;p class="abstract"&gt; &lt;/p&gt;

High-dose intravenous immunoglobulin is strongly associated with hemolytic anemia in patients with Kawasaki disease.

Hemolysis is a reported side effect of intravenous immunoglobulin (IVIG) therapy in adults, but pediatric data are scarce. We determined the frequency of IVIG-associated hemolysis in patients with Kawasaki disease (KD) and characterized risk factors for hemolysis. We hypothesized that hemolysis is more common in children with KD than adults with other disorders, and hemolysis risk is related to IVIG dose and degree of inflammation. This was an 8-year, single-center, retrospective cohort study. A total of 419 KD patients were identified; 123 had pre- and post-treatment complete blood counts allowing for assessment of anemia. Hemolytic anemia was defined as decrease in hemoglobin after IVIG greater than 1 g/dL with immunohematologic or biochemical studies supporting hemolysis. 123 patients were stratified as having hemolysis (n = 18, 15%) or nonhemolysis (n = 105, 85%). Patients with hemolysis were more likely to have complete versus incomplete KD (65% vs. 39%, p = 0.04) and refractory versus nonrefractory course (78% vs. 16%, p < 0.001). Patients receiving 4 g/kg versus 2 g/kg IVIG were more likely to hemolyze (89% vs. 34%, p < 0.001). Patients with hemolysis had mostly non-O blood group (94%), positive direct antiglobulin tests (89%), and positive eluates (72%). Two-thirds of patients with hemolysis required RBC transfusion. Hemolysis occurred in 15% of KD patients evaluated for anemia and is strongly associated with high-dose (4 g/kg) IVIG. KD patients receiving high-dose IVIG should have close hematologic monitoring to identify hemolysis.

Efficacy of two formulations of afoxolaner (NexGard\xae and NexGard Spectra\xae) for the treatment of generalised demodicosis in dogs, in veterinary dermatology referral centers in Europe

BackgroundA multi-centre field trial was conducted to evaluate the efficacy of afoxolaner based chewables (NexGard® or NexGard Spectra®) for the treatment of generalised demodicosis caused by Demodex canis in dogs under field conditions in France, Italy and Poland.MethodsClient-owned dogs, diagnosed positive for Demodex mites by pre-treatment skin scrapings and presenting clinical signs of generalised demodicosis were included. Dogs were orally treated with afoxolaner three times at monthly intervals. Of the 50 dogs enrolled, 48 completed the whole study. Efficacy of the treatments was assessed monthly by Demodex mite counts and physical examination with special regard to the severity and extension of skin lesions.ResultsTreatments were well tolerated in all dogs and resulted in a rapid reduction of mites, with all post-treatment mite counts significantly lower than baseline. The number of mites was reduced by 87.6%, 96.5% and 98.1% on Days 28, 56 and 84, respectively. In addition, the skin lesion severity and extent scores as well as the pruritus were all significantly lower at all post-treatment visits compared to the pre-treatment assessment.ConclusionsThis clinical field study demonstrated that monthly administrations of afoxolaner in NexGard® or NexGard Spectra®, offered a convenient and reliable solution for the treatment of canine generalised demodicosis.

Safety and efficacy of topical cantharidin for the treatment of pediatric molluscum contagiosum: a prospective, randomized, double-blind, placebo-controlled pilot trial.

Topical cantharidin is a commonly used treatment for molluscum contagiosum (MC). However, studies validating its safety and efficacy are limited. We conducted a 6-week, randomized, double-blind, placebo-controlled trial with subsequent open-label extension to assess the safety and effectiveness of cantharidin in treating pediatric MC. Ninety-four participants with MC were randomized to receive cantharidin or placebo, with or without occlusion. The primary outcome was complete lesion clearance. Secondary outcomes included post-treatment lesion count, adverse events, and side effects. No significant differences between the study arms, including baseline lesion count, were observed. The overall mean (SD) baseline lesion count was 22.2 (12.9). The number of participants achieving total clearance is as follows: 7/23 (30.4%) in the cantharidin only arm, 10/24 (41.7%) in the cantharidin with occlusion arm, 2/25 (8.0%) in the placebo with occlusion arm, and 3/22 (13.6%) in the placebo only arm. Post hoc analysis demonstrated that 17/47 (36.2%) participants in the combined cantharidin arms achieved clearance compared to 5/47 (10.6%) in the placebo arms (P=0.0065). The mean (SD) lesion count change from baseline was -5.1 (12.2) in the placebo only arm; the mean change (SD) was -17.4 (12.8) in the cantharidin only arm (P=0.0033) and -15.9 (11.6) in the cantharidin with occlusion arm (P=0.0101). No serious adverse events or side effects were observed. Topical cantharidin was well-tolerated and associated with the resolution of MC.

The Promise of Circulating Tumor Cells in Metastatic CRPC

The Promise of Circulating Tumor Cells in Metastatic CRPC